The aims of this proposal are: 1) To characterize the humoral and cellular immunology of cutaneous candidiasis in experimental mouse models, using normal and specifically immunodeficient inbred strains, and elucidate the role of immune mechanisms in the course of Candida infections; 2) To describe Candida derived enzyme factors which facilitate the organism's invasion through epidermal and dermal tissue of the skin, and promote inflammation; 3) To characterize the adherence property of Candida species to epidermal keratinocytes; and 4) To correlate the immune response of the host, and the enzymatic and adherence properties of Candida to the pathogenic potential of individual species, as demonstrated in the normal and immunodeficient murine models of candidiasis. This will be accomplished by studying primary and repeat infections in normal mice, and strains deficient in natural host immune resistance, including complement deficient, T cell lymphocyte defective, B cell lymphocyte defective, phagocyte defective, and drug-induced diabetes mellitus associated immune disorders. In vitro immune parameters of immunoglobulin synthesis, T cell responsiveness, and phagocyte function will be measured and correlated with the course and severity of the experimental disease. Saccharidase, lipase, and protease enzymes elaborated by Candida organisms will be assayed in 6 species, and will be correlated with the capability of these species to invade mouse cutaneous tissue and evoke inflammation in vivo. The adherence of Candida spp. blastospores and mycelia to dispersed mouse skin keratinocytes will be measured in vitro and correlated with cutaneous pathogenicity. The objectives of this proposal are to characterize the immune and inflammatory mediated events that are associated with cutaneous candidiasis, and the role these events play in the pathogenesis of the disease. The mechanism of Candida spp. invasion of the skin through endogenous enzymatic factors and adherence to skin cells are to be described. This proposal will utilize the disciplines of dermatology, microbiology, cellular and humoral immunology, and biochemistry to fulfill these objectives. The description and characterization of the pathogenic mechanisms of cutaneous candidiasis may help delineate critical steps that are amenable to therapeutic intervention, and provide a model for the study of infectious diseases of the skin.